Two amino acid mutation disrupts RORγt function in Th17 differentiation but not thymocyte development

• Published in: Nature immunology Vol. 18; no. 10; pp. 1128 - 1138
• Main Authors: He, Zhiheng, Ma, Jian, Wang, Ruiqing, Zhang, Jing, Huang, Zhaofeng, Wang, Fei, Sen, Subha, Rothenberg, Ellen V., Sun, Zuoming
• Format: Journal Article
• Language: English
• Published: 28.08.2017
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3832

RORγt regulates T H 17 differentiation, thymic T cell development and lymph node genesis. Although elimination of RORγt prevents T H 17-mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified two amino acid mutations in RORγt (RORγt M ) that preferentially disrupted T H 17 differentiation but not thymocyte development. Mice expressing RORγt M were resistant to EAE associated with defective T H 17 differentiation, but maintained normal thymocyte development and lymph node genesis, except for Peyer’s patches. RORγt M showed reduced ubiquitination at K69 that is selectively required for T H 17 differentiation but not T cell development. This study will inform the development of treatments that selectively target T H 17-mediated autoimmunity, but do not affect thymocyte development and induce lymphoma.